Centre for Cellular and Molecular Biology, (Council of Scientific and Industrial Research), Uppal Road, Tarnaka, Hyderabad 500007, India.
Centre for Cellular and Molecular Biology, (Council of Scientific and Industrial Research), Uppal Road, Tarnaka, Hyderabad 500007, India.
Gene. 2024 Jan 30;893:147958. doi: 10.1016/j.gene.2023.147958. Epub 2023 Nov 3.
Several covalent modifications are found associated with the transcriptionally active chromatin regions constituted by the genes transcribed by RNA polymerase (pol) II. Pol III-transcribed genes code for the small, stable RNA species, which participate in many cellular processes, essential for survival. Pol III transcription is repressed under most of the stress conditions by its negative regulator Maf1. We found that most of the histone acetylations increase with starvation-induced repression on several genes transcribed by the yeast pol III. On one of these genes, SNR6 (coding for the U6snRNA), a strongly positioned nucleosome in the gene upstream region plays regulatory role under repression. On this nucleosome, the changes in H3K9 and H3K14 acetylations show different dynamics. During repression, acetylation levels on H3K9 show steady increase whereas H3K14 acetylation increases with a peak at 40 min after which levels reduce. Both the levels settle by 2 hr to a level higher than the active state, which revert to normal levels with nutrient repletion. The increase in H3 acetylations is seen in the mutants reported to show reduced SNR6 transcription but not in the maf1Δ cells. This increase on a regulatory nucleosome may be part of the signaling mechanisms, which prepare cells for the stress-related quick repression as well as reactivation. The contrasting association of the histone acetylations with pol II and pol III transcription may be an important consideration to make in research studies focused on drug developments targeting histone modifications.
几种共价修饰与由 RNA 聚合酶(pol)II 转录的基因组成的转录活跃染色质区域相关。Pol III 转录的基因编码小而稳定的 RNA 种类,这些 RNA 参与许多细胞过程,对生存至关重要。在大多数应激条件下,Pol III 转录受到其负调节剂 Maf1 的抑制。我们发现,在酵母 pol III 转录的几个基因中,饥饿诱导的抑制会导致大多数组蛋白乙酰化增加。在这些基因中的一个基因 SNR6(编码 U6snRNA)中,在基因上游区域中具有强烈定位的核小体在抑制下发挥调节作用。在这个核小体上,H3K9 和 H3K14 乙酰化的变化显示出不同的动态。在抑制过程中,H3K9 上的乙酰化水平稳定增加,而 H3K14 乙酰化在 40 分钟后增加,然后水平降低。这两种水平在 2 小时后稳定在高于活跃状态的水平,在营养补充后恢复正常水平。在报道的 SNR6 转录减少的突变体中可以看到 H3 乙酰化的增加,但在 maf1Δ 细胞中则没有。这种在调节核小体上的增加可能是细胞为应激相关的快速抑制以及重新激活做准备的信号机制的一部分。Pol II 和 pol III 转录的组蛋白乙酰化的对比关联可能是针对组蛋白修饰的药物开发研究中需要考虑的一个重要因素。